Reactive oxygen species and redox compartmentalization

Abstract

Reactive oxygen species (ROS) formation and signaling are of major importance and regulate a number of processes in physiological conditions. A disruption in redox status regulation, however, has been associated with numerous pathological conditions. In recent years it has become increasingly clear that oxidative and reductive modifications are confined in a spatio-temporal manner. This makes ROS signaling similar to that of Ca2+ or other second messengers. Some subcellular compartments are more oxidizing (such as lysosomes or peroxisomes) whereas others are more reducing (mitochondria, nuclei). Moreover, although more reducing, mitochondria are especially susceptible to oxidation, most likely due to the high number of exposed thiols present in that compartment. Recent advances in the development of redox probes allow specific measurement of defined ROS in different cellular compartments in intact living cells or organisms. The availability of these tools now allows simultaneous spatio-temporal measurements and correlation between ROS generation and organelle and/or cellular function. The study of ROS compartmentalization and microdomains will help elucidate their role in physiology and disease. Here we will examine redox probes currently available and how ROS generation may vary between subcellular compartments. Furthermore, we will discuss ROS compartmentalization in physiological and pathological conditions focusing our attention on mitochondria, since their vulnerability to oxidative stress is likely at the basis of several diseases.

Cell stress increases ATP release in NLRP3 inflammasome-mediated autoinflammatory diseases, resulting in cytokine imbalance

“…Why and how mutations cause cell stress is unclear. Because mitochondria are the first target of ROS, and their oxidation further induces ROS production (35), it is conceivable that mitochondria-derived ROS contribute a great extent to cell stress in autoinflammatory diseases. In agreement, the involvement of mitochondrial ROS have been proposed in TRAPS (17) and in CAPS (18).…”

Mitochondrial calcium overload is a key determinant in heart failure

“…Oxidative overload in cardiomyocytes originates from multiple sources, including mitochondria, NAD(P)H oxidase, xanthine oxidase, and uncoupled nitric oxide synthase (16,25,26). Mitochondrial-derived ROS are elevated during cardiac overload or ischemic stress (4,26,27).…”

“…Mitochondrial-derived ROS are elevated during cardiac overload or ischemic stress (4,26,27). Mitochondrial membrane potential, Δψ m , is closely linked to Ca 2+ levels and to mitochondrial ROS production; indeed, depolarized mitochondria produce more ROS, leading to further organelle depolarization, resulting in a vicious cycle.…”

Biological Effectiveness of Ionizing Radiation: Acute vs. Protracted Exposures

“…Given the evolutionary prerequisite of best fitness, it would be reasonable to assume that living organisms have been adapted by the natural selection to background levels of ionizing radiation [10]. Accordingly, there must be an optimal exposure level, as it is for many environmental factors: visible and ultraviolet light, different chemical elements and compounds [11], as well as the products from radiolysis of water [12]. Evolutionary adaptation to a changing environmental factor would lag behind its current value and correspond to some average of historic levels.…”